Aging is associated with a loss of brain neurotransmitter function. The loss of cholinergic neurons apparently parallels the loss of cognitive function. We found that IP administration of GM1 ganglioside, a normal constituent of brain membranes, enhanced acetylcholine (ACh) content in the striatum and choline uptake in the striatum and hippocampus of old (22-24 month old) rats, but had no effect in young rats. GM1 administered by intracerebroventricular (ICV) infusion also increased the aforementioned cholinergic markers as well as increased choline acetyltransferase (ChAT) activity in the striatum of old rats. The improvement of cholinergic neurochemistry was accompanied by improvement of approach/avoidance learning in the old animals. Nerve growth factor (NGF) given ICV induced similar biochemical responses. Co-administration of NGF and GM1 appeared to be more effective than either alone for enhancing ChAT activity in striatum. Since GM1 and NGF induce similar responses on cholinergic neurochemical markers in old animals, we postulate that there may be a common link between them. The goals of this proposal are to: (1) explore the consequences of administering GM1 on cholinergic parameters in the brain of aged rats; (2) investigate the fate of the exogenously administered GM1; (3) to study whether there is an interaction between GM1 and NGF responsive systems. Our findings suggest that GM1 may have significant therapeutic potential for treating the neurochemical deficits and the loss of cognitive ability associated with aging.